The focus of attention in recent years has been on imaging mass spectrometry (IMS), particularly with high spatial resolution with the objective of analyzing μm- or even sub-μm scale structures such as cell organelles.
Laser ablation combined with inductively coupled plasma mass spectrometry (LA-ICP-MS) can be used for trace element mapping. This, however, only provides spatial resolution limited by the laser sampling spot size and the analyte concentration.
The ICP ion source is also an atomizer which destroys all molecular information. For molecular mass spectrometry, another technique called matrix-assisted laser desorption ionization (MALDI) has been developed. This method requires a delicate chemical and physical sample manipulation which prevents the study of live specimens. This technique requires, for example, that a matrix substance be applied to the sample surface to facilitate the desorption process of the analyte molecules from the surface. The method, which is particularly successful for thin tissue sections, requires that a relatively thick, very uniform layer of matrix material to be applied, for example, by spraying as a solution in individual layers. The matrix material must further be selected to interact with the wavelength of the laser, and must be suitable to support the desorption of the target analyte molecules. A disadvantage of the applied matrix layer is the loss of lateral spatial resolution. In order to benefit from the possible spatial resolution of laser sampling, the deteriorating washing effect by the applied matrix must be avoided.
While the laser ablation system for LA-ICP-MS is a unit that is connected to the ICP-MS via a transfer line, the laser desorption unit of an MALDI-MS must be placed at a very short distance to the sampling interface of the mass spectrometer. Since the distance between the sample surface and the sampling interface of the mass spectrometer is critical, a dedicated MALDI-MS instrument, or at least a dedicated source incorporating the laser desorption, is required.
Another technique, termed laser ablation electrospray ionization (LAESI), requires no sample pretreatment, can operate at atmospheric pressure, and offers the potential of depth information. In this technique, laser ablation using a mid-IR laser removes material from a surface and electrospray ionization (ESI) is used to directly ionize molecules from the ablation plume. At least the ionization source is here also a dedicated construction incorporating the laser sampler.
Existing techniques for laser ablation/desorption for molecular mass spectrometry require dedicated instruments or at least dedicated sources incorporating the laser desorption unit in very close connection to the sample entrance of the mass spectrometer. Possibilities for quantification are limited because the sensitivity of these techniques is dependent on the analytes used, and on the matrix and topography of the sample. LA-ICP-MS does, however, provide good possibilities to quantify an elemental composition.
Another hot topic in mass spectrometry is the simultaneous acquisition of both molecular and elemental information for structure elucidation and elemental composition quantification. While past use of ICP-MS and ESI-MS focused on the competition of the two techniques, the complementary information gained by the two techniques was subsequently valued. The first parallel and simultaneous use of two types of mass spectrometers was realized for sample introduction by means of high pressure liquid chromatography (HPLC), and has since then has been used by many researchers. The parallel use of two mass spectrometers has since been realized for gaseous samples being eluted from a gas chromatograph. Special routines to compare, synchronize, and merge the data from the two mass spectrometers have been developed. The integration of two types of mass spectrometers for the quasi-simultaneous acquisition of atomic and molecular mass spectra has also previously been described.